DESCRIPTION: The long-term objective of this project is to engineer biological tooth substitutes that can be used to replace missing, diseased or injured human teeth. The approach, based on recent successful tissue engineering efforts, is to seed single cell suspensions derived from immature tooth buds onto biodegradable polymer scaffolds, and to implant the seeded scaffolds in the omentum of rat hosts to support their growth into highly ordered tooth structures. Currently, it is possible to reproducibly bioengineer small tooth crowns containing dentin, enamel and cementum, using tooth bud cells obtained from both rats and pigs. The results are the first to demonstrate the utility of this method to grow tooth structures containing mature dentin and enamel from undifferentiated, cultured tooth bud cells, and suggest the presence of both epithelial and mesenchymal Dental stem cells in the tooth bud cell populations. Currently, the bioengineered tooth structures are quite small and do not acquire the shape of the scaffold onto which the cell suspensions are seeded. The successful clinical application of this method demands an ability to manipulate the size and shape of the bioengineered teeth. Based on preliminary results, and on a desire to generate bioengineered teeth with clinical relevance, the following studies are proposed. The proposed Aims are to: 1) Establish a correlation between cell seeding density and bioengineered tooth size; and 2) Correlate biodegradable scaffold shape with bioengineered tooth shape. Completion of the proposed studies will lead to the generation of bioengineered teeth for eventual use in clinical applications in humans. The proposed studies will facilitate tooth tissue engineering efforts by elucidating the manner by which tooth bud cell interactions with biodegradable scaffold matrix result in the formation of teeth of predetermined size and shape.